The online version of this article (doi:10.1186/1476-9255-9-7) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
MZ and MWK carried out all animal work, immunocytochemistry (i.e., high throughput and confocal imaging) and flow cytometry experiments. Additionally, MZ and MWK gathered the raw data and using statistical analyses and graphic programs compiled the data into meaningful information. MZ, MWK, JLO also contributed to writing the Methods section of the manuscript. MZ and MWK collected all of the graphics and formed the figures of the Manuscript. YJG, TK designed experiments and contributed to writing the Methods section. KS performed Slp proteome analysis on NCK2031 strain. MM designed experiments, discussed and wrote the manuscript. All authors have read and approved this manuscript.
The cellular and molecular mechanisms of inflammatory bowel disease are not fully understood; however, data indicate that uncontrolled chronic inflammation induced by bacterial gene products, including lipoteichoic acid (LTA), may trigger colonic inflammation resulting in disease pathogenesis. LTA is a constituent glycolipid of Gram-positive bacteria that shares many inflammatory properties with lipopolysaccharide and plays a critical role in the pathogenesis of severe inflammatory responses via Toll-like receptor 2. Accordingly, we elucidate the role of LTA in immune stimulation and induced colitis in vivo.
To better understand the molecular mechanisms utilized by the intestinal microbiota and their gene products to induce or subvert inflammation, specifically the effect(s) of altered surface layer protein expression on the LTA-mediated pro-inflammatory response, the Lactobacillus acidophilus s urface l ayer p rotein (Slp) genes encoding SlpB and SlpX were deleted resulting in a SlpB- and SlpX- mutant that continued to express SlpA (assigned as NCK2031).
Our data show profound activation of dendritic cells by NCK2031, wild-type L. acidophilus (NCK56), and purified Staphylococcus aureus-LTA. In contrary to the LTA-deficient strain NCK2025, the LTA-expressing strains NCK2031 and NCK56, as well as S. aureus-LTA, induce pro-inflammatory innate and T cell immune responses in vivo. Additionally, neither NCK2031 nor S. aureus-LTA supplemented in drinking water protected mice from DSS-colitis, but instead, induced significant intestinal inflammation resulting in severe colitis and tissue destruction.
These findings suggest that directed alteration of two of the L. acidophilus NCFM-Slps did not ameliorate LTA-induced pro-inflammatory signals and subsequent colitis.
Authors’ original file for figure 112950_2011_225_MOESM1_ESM.jpeg
Authors’ original file for figure 212950_2011_225_MOESM2_ESM.jpeg
Authors’ original file for figure 312950_2011_225_MOESM3_ESM.jpeg
Authors’ original file for figure 412950_2011_225_MOESM4_ESM.jpeg
Authors’ original file for figure 512950_2011_225_MOESM5_ESM.jpeg
Authors’ original file for figure 612950_2011_225_MOESM6_ESM.jpeg
Reichmann NT, Grundling A: Location, synthesis and function of glycolipids and polyglycerolphosphate lipoteichoic acid in Gram-positive bacteria of the phylum Firmicutes. FEMS MicrobiolLett. 2011, 319: 97-105. 10.1111/j.1574-6968.2011.02260.x. CrossRef
Su SC, Hua KF, Lee H, Chao LK, Tan SK, Yang SF, et al: LTA and LPS mediated activation of protein kinases in the regulation of inflammatory cytokines expression in macrophages. ClinChimActa. 2006, 374: 106-115.
Chang HC, Lin KH, Tai YT, Chen JT, Chen RM: Lipoteichoic acid-induced TNF-alpha and IL-6 gene expressions and oxidative stress production in macrophages are suppressed by ketamine through downregulating Toll-like receptor 2-mediated activation oF ERK1/2 and NFkappaB. Shock. 2010, 33: 485-492. CrossRefPubMed
Kengatharan KM, De Kimpe S, Robson C, Foster SJ, Thiemermann C: Mechanism of gram-positive shock: identification of peptidoglycan and lipoteichoic acid moieties essential in the induction of nitric oxide synthase, shock, and multiple organ failure. J Exp Med. 1998, 188: 305-315. 10.1084/jem.188.2.305. PubMedCentralCrossRefPubMed
Mohamadzadeh M, Pfeiler EA, Brown JB, Zadeh M, Gramarossa M, Managlia E, et al: Regulation of induced colonic inflammation by Lactobacillus acidophilus deficient in lipoteichoic acid. Proc NatlAcadSci USA. 2011, 108: 4623-4630. 10.1073/pnas.1005066107. CrossRef
Goh YJ, Azcarate-Peril MA, O'Flaherty S, Durmaz E, Valence F, Jardin J, et al: Development and application of a upp-based counterselective gene replacement system for the study of the S-layer protein SlpX of Lactobacillus acidophilus NCFM. Appl Environ Microbiol. 2009, 75: 3093-3105. 10.1128/AEM.02502-08. PubMedCentralCrossRefPubMed
Sallusto F, Lanzavecchia A: Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha. J Exp Med. 1994, 179: 1109-1118. 10.1084/jem.179.4.1109. CrossRefPubMed
Mohamadzadeh M, Olson S, Kalina WV, Ruthel G, Demmin GL, Warfield KL, et al: Lactobacilli activate human dendritic cells that skew T cells toward T helper 1 polarization. Proc NatlAcadSci USA. 2005, 02 (8): 2880-2885. CrossRef
Cooper HS, Murthy SN, Shah RS, Sedergran DJ: Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest. 1993, 69: 238-249. PubMed
Kaji R, Kiyoshima-Shibata J, Nagaoka M, Nanno M, Shida K: Bacterial teichoic acids reverse predominant IL-12 production induced by certain lactobacillus strains into predominant IL-10 production via TLR2-dependent ERK activation in macrophages. J Immunol. 2010, 184: 3505-3513. 10.4049/jimmunol.0901569. CrossRefPubMed
Fleissner D, Frede A, Knott M, Knuschke T, Geffers R, Hansen W, et al: Generation and function of immunosuppressive human and murine CD8(+) T cells by transforming growth factor-beta and retinoic acid. Immunol. 2011, 134: 82-92. 10.1111/j.1365-2567.2011.03469.x. CrossRef
Simpson SJ, Shah S, Comiskey M, de Jong YP, Wang B, Mizoguchi E, et al: T cell-mediated pathology in two models of experimental colitis depends predominantly on the interleukin 12/Signal transducer and activator of transcription (Stat)-4 pathway, but is not conditional on interferon gamma expression by T cells. J Exp Med. 1998, 187: 1225-1234. 10.1084/jem.187.8.1225. PubMedCentralCrossRefPubMed
Kullberg MC, Rothfuchs AG, Jankovic D, Caspar P, Wynn TA, Gorelick PL, et al: Helicobacter hepaticus-induced colitis in interleukin-10-deficient mice: cytokine requirements for the induction and maintenance of intestinal inflammation. Infect Immun. 2001, 69: 4232-4241. 10.1128/IAI.69.7.4232-4241.2001. PubMedCentralCrossRefPubMed
Pallone F, Fina D, Caruso R, Monteleone G: Role of IL-21 in inflammatory bowel disease. Expert Rev ClinImmunol. 2010, 6: 537-541. CrossRef
Miyauchi E, Morita H, Okuda J, Sashihara T, Shimizu M, Tanabe S: Cell wall fraction of Enterococcus hirae ameliorates TNF-alpha-induced barrier impairment in the human epithelial tight junction. LettApplMicrobiol. 2008, 46: 469-476.
Billiau A, Heremans H, Vandekerckhove F, Dijkmans R, Sobis H, Meulepas E, et al: Enhancement of experimental allergic encephalomyelitis in mice by antibodies against IFN-gamma. J Immunol. 1988, 140: 1506-1510. PubMed
Manoury-Schwartz B, Chiocchia G, Bessis N, Abehsira-Amar O, Batteux F, Muller S, et al: High susceptibility to collagen-induced arthritis in mice lacking IFN-gamma receptors. J Immunol. 1997, 158: 5501-5506. PubMed
Konstantinov SR, Smidt H, de Vos WM, Bruijns SC, Singh SK, Valence F, et al: S layer protein A of Lactobacillus acidophilus NCFM regulates immature dendritic cell and T cell functions. Proc NatlAcadSci USA. 2008, 105: 19474-19479. 10.1073/pnas.0810305105. CrossRef
- Induction of intestinal pro-inflammatory immune responses by lipoteichoic acid
Mohammad W Khan
Yong Jun Goh
Jennifer L Owen
- BioMed Central
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
Mail Icon II